Nod2 is Required for Normal Alveolar Macrophage TNF-α. Secretion i.n Response to P. aeruginosa Challenge: a Crucial Innate Immune Receptor in Lung Infection
Loading...
Authors
Stoolman, Joshua
Issue Date
2008
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Early detection of pathogens and subsequent regulation of the immune response
are crucial to protect the lungs against harmful pathogens. These tasks are carried out by
mechanisms of innate immunity, the body's initial non-specific defense against invading
pathogens. A group of proteins involved in non-specific immunity are the Pattern
Recognition Receptors (PRRs) such as the Toll-like Receptors (TLRs) and Nod-like
Receptors (NLRs) that detect parts of invading pathogens called Pathogen Associated
Molecular Patterns (PAMPs). Detection of the P AMPs by PRRs can cause production
and secretion pro-inflammatory molecules such as Tumor Necrosis Factor (TNF-α.) or
activation apoptotic signaling pathways via downstream clevage of inactive, proapoptotic
caspases. Nucleotide-binding oligomerization domain containing 1 and 2
receptors (NodI and Nod2), members of the NLR family of proteins that detect PAMPs
in the cytosol, have been documented as essential in the maintenance of intestinal
microflora through activity in intestinal epithelial cells. They are also expressed in
alveolar macrophages (AM) and alveolar epithelial cells (AEC), the major proinflammatory
molecule secreting cells of the lung. Primary culture alveolar macrophages
(AM) and alveolar epithelial cells (AEC) from Wild Type (WT) and NodI and/or Nod2
knockout mice were challenged with purified PRR stimulating molecules or
Pseudomonas aeruginosa, an opportunistic bacteria known to cause serious infections in
immunocompromised patients. AM and AEC TNF-α. secretion was measured by ELISA.
Nod2 and double knockout AM showed a decrease in TNF-a. production compared to
WT AM. AEC chemokine expression was elevated in the presence of TLR ligands co-stimulated with NodI or Nod2 ligands. The Data shows a crucial role for Nod2 in the
production of pro-inflammatory master cytokine TNF-α, Implicating the receptor as a
crucial mediator for initial detection and response to invasive P. aeruginosa.
Description
vi, 34 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.